TY - JOUR
T1 - Regulation of immunity and disease resistance by commensal microbes and chromatin modifications during zebrafish development
AU - Galindo-Villegas, Jorge
AU - Garciá-Moreno, Diana
AU - De Oliveira, Sofia
AU - Meseguer, José
AU - Mulero, Victoriano
PY - 2012/9/25
Y1 - 2012/9/25
N2 - How fish larvae are protected frominfection before the maturation of adaptive immunity, a process which may take up to several weeks in most species, has long been a matter of speculation. Using a germ-free model, we show that colonization by commensals in newly hatched zebrafish primes neutrophils and induces several genes encoding proinflammatory and antiviral mediators, increasing the resistance of larvae to viral infection. Commensal microbe recognition was found to be mediated mainly through a TLR/MyD88 signaling pathway, and professional phagocytes were identified as the source of these immunemediators. However, the induction of proinflammatory and antiviral genes, but not of antimicrobial effector genes, also required the covalent modification of histone H3 at gene promoters. Interestingly, chromatin modifications were not altered by commensal microbes or hatching. Taken together, our results demonstrate that gene-specific chromatin modifications are associated with the protection of zebrafish larvae against infectious agents before adaptive immunity has developed and prevent pathologies associated with excessive inflammation during development.
AB - How fish larvae are protected frominfection before the maturation of adaptive immunity, a process which may take up to several weeks in most species, has long been a matter of speculation. Using a germ-free model, we show that colonization by commensals in newly hatched zebrafish primes neutrophils and induces several genes encoding proinflammatory and antiviral mediators, increasing the resistance of larvae to viral infection. Commensal microbe recognition was found to be mediated mainly through a TLR/MyD88 signaling pathway, and professional phagocytes were identified as the source of these immunemediators. However, the induction of proinflammatory and antiviral genes, but not of antimicrobial effector genes, also required the covalent modification of histone H3 at gene promoters. Interestingly, chromatin modifications were not altered by commensal microbes or hatching. Taken together, our results demonstrate that gene-specific chromatin modifications are associated with the protection of zebrafish larvae against infectious agents before adaptive immunity has developed and prevent pathologies associated with excessive inflammation during development.
KW - Cytokines
KW - Epigenetic
KW - Evolution
KW - Gene regulation
KW - Live imaging
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U2 - 10.1073/pnas.1209920109
DO - 10.1073/pnas.1209920109
M3 - Article
C2 - 22949679
AN - SCOPUS:84866846963
SN - 0027-8424
VL - 109
SP - E2605-E2614
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 39
ER -